DESCRIPTION (Verbatim from the application): Multipotent stem cells exist in a variety of embryonic and post-embryonic tissues, and include neural and hematopoietic stem cells. These cells, which have the ability to both self-renew and differentiate in response to biological stimuli, hold great potential for replacing damaged or diseased tissues. The greatest utility for such cells will be in their application to the treatment of cardiovascular disease. Specifically, hemangioblastic stem cells will provide for cellular angiogenic therapy, and allow modulation of the immune system for cardiac xenotransplantation. There is mounting evidence that human and mouse hemangioblasts exist in embryonic life and may persist into adulthood. Understanding the conditions which control their expansion and differentiation would facilitate direct investigation of these cells in treating pathologic conditions. The full therapeutic potential of stem cells can only be realized if they are characterized and isolated to near homogeneity in animal models relevant to human disease. We propose to isolate and characterize hemangioblasts from pigs by cloning and developing antibodies to highly conserved stem cell markers. The pig has distinct advantages in applied animal research because of its size, hemodynamic similarity to humans, and breeding characteristics. Pigs are used extensively to test percutaneous vascular interventions, and they are also the most likely animal source for organ xenotransplantation. The specific aims of this proposal are: 1) To isolate pig blood and bone marrow cells which lack features of terminal differentiation, and which express hemagioblast-associated surface antigens using newly generated pig-specific antibodies. Isolated cell populations will be adapted to culture. 2) To characterize the vascular and hematopoietic potential of the above isolated cell populations in vitro, and assess their self-renewing potential.